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Cyclic adenosine monophosphate involvement in low-dose cyclophosphamide-reversed immune evasion in a mouse lymphoma model

Cellular & Molecular Immunology volume 9, pages 482–488 (2012)Cite this article

Abstract

Lymphoma cells mobilize many mechanisms to evade the immune system. There is substantial evidence that CD4+CD25+ regulatory T cells (Tregs) play a key role in the control of immune evasion. Tregs can transfer cyclic adenosine monophosphate (cAMP) to effector T cells, suggesting an association between Tregs' immune-evasion role and the intracellular cAMP pathway. In this study, we used A20 B-cell lymphoma mice as aggressive tumor models to investigate the mechanism of the depletion of Tregs by low-dose cyclophosphamide (CY, 20 mg/kg). The tumor-bearing mice had longer survival times and slower tumor growth rates following treatment with CY, but its effects were temporary. Along with the depletion of Tregs by low-dose CY treatment, the expression of interleukin-2 (IL-2) in T effector cells increased, and intracellular cAMP concentrations in immune cells decreased. Our study demonstrates the ability of low-dose CY to reverse Tregs-mediated immune evasion in a mouse model. The changes in intracellular cAMP concentrations correlated with the upregulation of effector T cells and the downregulation of Tregs, indicating the close association of cAMP analogs and low-dose CY in the immune therapy of B-cell lymphoma.

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Acknowledgements

This study was supported by grants from the Natural Science Foundation of Shandong Province, China (Nos. Y2007C053 and ZR2009CM059), the Scientific and Technological Project of Shandong Province, China (Nos. 2007GG10002008, 2008GG2NS02018 and 2010GSF10250), the Taishan Scholar Program (2011) and the Program of Shandong Medical Leading Talent (2009). We thank the technicians from the research center and animal facility of Shandong Provincial Hospital for their assistance in conducting this research. We also thank Dr Bin Chen and Caocao Wei for critically reading the manuscript.

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Authors and Affiliations

  1. Department of Hematology, Provincial Hospital Affiliated to Shandong University, Jinan, China

    Ai-Xia Dou, Li-Li Feng, Xiao-Qian Liu & Xin Wang

  2. Department of Hematology, Second Hospital of Shandong University, Jinan, China

    Ai-Xia Dou

  3. Department of Diagnostics, Shandong University School of Medicine, Jinan, China

    Xin Wang

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Correspondence to Xin Wang.

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Dou, AX., Feng, LL., Liu, XQ. et al. Cyclic adenosine monophosphate involvement in low-dose cyclophosphamide-reversed immune evasion in a mouse lymphoma model. Cell Mol Immunol 9, 482–488 (2012). https://doi.org/10.1038/cmi.2012.34

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